The present invention relates to a kit for producing bone cement and a method for producing bone cement.
Conventional poly(methylmethacrylate) bone cements (PMMA bone cements) have been known for decades and are based on the ground-breaking work of Sir Charnley (Charnley, J., “Anchorage of the Femoral Head Prosthesis of the Shaft of the Femur, J. Bone Joint Surg. 42:28-30 (1960)). The basic structure of PMMA bone cements has remained the same ever since. PMMA bone cements consist of a liquid monomer component and a powder component. The monomer component generally contains (i) the monomer, methylmethacrylate, and (ii) an activator (e.g. N,N-dimethyl-p-toluidine) dissolved therein. The powder component comprises (i) one or more polymers that are made by polymerization, preferably suspension polymerization, based on methylmethacrylate and co-monomers, such as styrene, methylacrylate or similar monomers, (ii) a radio-opacifier, and (iii) an initiator, (e.g. dibenzoylperoxide). Mixing the powder component and the monomer component, the polymers of the powder component in the methylmethacrylate swell, which generates a dough that can be shaped plastically. Simultaneously, the activator, N,N-dimethyl-p-toluidine, reacts with dibenzoylperoxide, which disintegrates and forms radicals in the process. The radicals thus formed trigger the radical polymerization of the methylmethacrylate. Upon advancing polymerization of the methylmethacrylate, the viscosity of the cement dough increases until the cement dough solidifies and thus is cured.
The underlying mechanical requirements of PMMA bone cements, such as 4-point flexural strength, flexural modulus, and compressive strength, are described in ISO 5833. The property of PMMA bone cement to be non-tacky is of essential importance to users of PMMA bone cements. The term “non-tackiness” is defined in ISO 5833 and indicates that the PMMA bone cement has reached the processing phase in the monomer after mixing of the components owing to swelling of the polymers present in the cement powder. A PMMA bone cement must be non-tacky as a matter of principle in order for the user to be able to shape and apply the cement. The PMMA bone cement must not stick to the gloves and application aids, such as mixing systems, crucibles or spatulas.
The essential disadvantage of the previous PMMA bone cements for the medical user is that the user needs to mix the liquid monomer component and the powder component in a mixing system or in crucibles right before applying the cement. Mixing errors can easily occur in the process and adversely affect the quality of the cement. Moreover, the components must be mixed rapidly. In this context, it is important to mix all of the cement powder and monomer component without forming lumps and prevent the introduction of air bubbles during the mixing process. Unlike manual mixing, the use of vacuum mixing systems prevents the formation of air bubbles in the cement dough to a large extent. Examples of mixing systems are disclosed in U.S. Pat. No. 4,015,945, European patent application publication EP 0674888 A1, and Japanese patent application publication (Kokai) JP 2003181270A. However, vacuum mixing systems necessitate an additional vacuum pump and are therefore relatively expensive. Moreover, depending on the type of cement concerned, a certain waiting time is required after mixing the monomer component and the powder component until the cement dough is tack-free and can be applied. Because of the large variety of errors that can occur while mixing conventional PMMA bone cements, appropriately trained personnel are required for this purpose. The corresponding training is associated with considerable expenses. Moreover, mixing of the liquid monomer component and the powder component is associated with exposure of the user to monomer vapors and particles released from the powder-like cement. Another essential disadvantage of conventional PMMA bone cements is that both the powder component and the monomer component each need to be manufactured in a doubly sterile-packaged manner, which requires at least four sterile packaging means for each package of bone cement.
German Patent DE 10 2007 050 762 B3 proposes a bone cement comprising two pastes as an alternative to conventional powder-liquid polymethylmethacrylate bone cements. These pastes each contain a methacrylate monomer for radical polymerization, a polymer soluble in the methacrylate monomer, and a particulate polymer insoluble in the methacrylate monomer. In addition, one of the pastes contains a radical polymerization initiator, whereas the other paste comprises a polymerization activator. As a result of the selected composition, the bone cement produced from the pastes possesses sufficiently high viscosity and cohesion in order to withstand the pressure from bleeding until it is fully cured. When the two pastes are mixed, the polymerization initiator reacts with the accelerator to form radicals that initiate the radical polymerization of the methacrylate monomers. Owing to the advancing polymerization, the paste is cured while the methacrylate monomers are consumed. It has been found that, even if highly cross-linked poly(methacrylate) particles are used as particulate polymer insoluble in the methacrylate monomer, these take up and enclose small fractions of methacrylate monomer and compounds dissolved therein. This causes the insoluble polymer particles of the one paste to contain inclusions of monomer liquid and initiator dissolved therein, whereas the insoluble polymer particles of the other paste in turn contain inclusions of monomer liquid and accelerator dissolved therein. After the two pastes are mixed, the phase consisting of the methacrylate monomer and the polymer dissolved therein, in which the insoluble polymer particles are suspended, cures while forming bone cement that is ready for application. Afterwards, the initially enclosed monomer liquid diffuses from the insoluble polymer particles and undergoes secondary polymerization. The monomer liquid diffusing from the insoluble polymer particles acts as a plasticizer, due to the secondary polymerization, until it is consumed. This leads to the initially cured bone cement pastes meeting the requirements of ISO 5833, but also still showing pronounced secondary curing due to secondary polymerization of the monomer liquid diffusing from the insoluble polymer particles.